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Endothelins Inhibit Luteinization of Cultured Porcine Granulosa Cells^*

Department of Gynecology & Obstetrics, Faculty of Medicine, Second Division, Department of Medicine (K.N., H.I.); Institute for Immunology, Faculty of Medicine (S.N.), Kyoto University Kyoto, Japan

Address requests for reprints to: Dr. Masazumi Iwai, Department of Gynecology & Obstetrics, Faculty of Medicine, Kyoto University, Sakyoku Kyoto, 606, Japan.

Abstract

Endothelin (ET), a novel vasoconstrictor peptide containing three isopeptides [ET-1, ET-2, and ET-3 (ETs)], has various biological effects including vasoconstriction, mitogenesis, and steroidogenesis. We examined the ET-1-like immunoreactivity level in porcine follicular fluid and culture medium of porcine granulosa cells by RIA. The ET level in the follicular fluid was 9.4-14.2 pg/ml. These levels were within 0.42 to 0.62-fold of the poicine plasma level (22.7 ± 3.1 pg/ml) (mean ± SE). ET was detected in the culture medium of granulosa cells with and without LH treatment at the concentration of 56 ± 9.3 and 4.9 ± 1.2 pg/10⁶ cells h, respectively. We also examined whether ETs affect the luteinization of granulosa cells. ETs inhibited the LH-stimulated progesterone and cAMP accumulation in cultured porcine granulosa cells in a dose-dependent manner with an EC₅₀ of 5 x 10^-11 M. ET-1, ET-2, and ET-3 (5 x 10^-8 M) inhibited progesterone accumulation by 62.3 ± 1.8, 59.8 ± 4.0, and 63.3 ± 5.7% in 6-day cultures, respectively, and significant inhibition was observed within 24 h of culture. ET- 1, ET-2, and ET-3 (5 x 10^-8 M) inhibited the LH-stimulated cAMP accumulation in granulosa cells by 54.8 ± 2.3, 55.4 ± 7.1, and 55.5 ± 6.2%, respectively, whereas they did not affect basal cAMP levels. As well as progesterone accumulation, ETs partially inhibited LH-stimulated morphological transformation of granulosa cells.

In this study, we demonstrated that ET exists in follicular fluid and in the culture medium of granulosa cells, and that ET inhibited LH-induced progesterone accumulation, morphological transformation, and cAMP accumulation in cultured porcine granulosa cells. These findings suggest that ET acts as a modulator of Steroid metabolism in preovulatory follicles. (Endocrinology 129: 1909–1914, 1991)

Footnotes

^* This work was supported in part by research grants from the Ministry of Education, Science and Culture of Japan.

Received April 11, 1991.

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